This section provides background information related to the present disclosure which is not necessarily prior art.
In the United States in 2014, there were 47,055 drug overdose deaths in the United States, representing a 6.5% increase from 2013 as reported by Rudd et al. (2016) Morbidity & Mortality Weekly Report 64(50):1378-82 (starting at page 10) “Increases in Drug and Opioid Overdose Deaths—United States, 2000-2014.”
As reported in the New York Times (6 Sep. 2016, page A10, headline “Cincinnati Is Awash With a Drug That Kills in Minuscule Doses”), an increasing and more intractable share of these overdoses relate to synthetic opium derivatives belonging to the fentanyl class. Fentanyl is about 50-100 times more powerful than heroin, and some fentanyl derivatives, such as carfentanyl, are about 100 times more powerful than fentanyl and 10,000 times more powerful that heroin (diamorphine). Overdoses from these fentanyl derived opioids have proven correspondingly harder to treat.
Naloxone is an opioid receptor antagonist that is approved for use by injection for the reversal of opioid overdose and for adjunct use in the treatment of septic shock. It is currently being used mainly in emergency departments and in ambulances by trained medical professionals. There have been efforts to expand its use by providing the drug to some patients with take-home opioid prescriptions and those who inject illicit drugs, potentially facilitating earlier administration of the drug. The proper use of naloxone is important. Firstly, if an inadequate dose is administered, the patient may either not recover from the opioid overdose, or may recover only to lapse back into overdose as effect of naloxone wears off. The half life of naloxone is shorter than certain opioids. In addition, some drug users administer a very small naloxone dose in order to reverse an overdose in a manner that minimizes naloxone's effect. This partial reversal of overdose can be very dangerous, given naloxone's relatively short half-life. This sort of titration away from overdose can end in the drug user's injury or death because of the failure to administer a sufficient naloxone does in time.
Meanwhile, the use of nasal naloxone is not without controversy. For instance, Dowling et al. (Ther Drug Monit, Vol 30, No 4, August 2008) reported that naloxone administered intranasally displays a relative bioavailability of 4% only and concluded that the IN absorption is rapid but does not maintain measurable concentrations for more than an hour.
U.S. Pat. No. 9,192,570 to Wyse reports naloxone formulations for intranasal administration. Wyse reports (column 27, lines 29-37) that benzalkonium chloride is not suitable in such formulations, because it facilitates unacceptable degradation of the naloxone. Wyse recommends (lines 41-43) benzyl alcohol and paraben preservatives in place of benzalkonium chloride.